Effect of different FSH isoforms on cyclic-AMP production by mouse cumulus-oocyte-complexes: a time course study.

The ability of different isoforms of follicle stimulating hormone (FSH) to induce accumulation of cAMP in cultured mouse cumulus-oocyte-complexes (COC) was evaluated in a time course study. Using isoform fractions representing less acidic (pI 6.43-5.69), mid-acidic (pI 5.62-4.96) and acidic (pI 4.69-3.75) isoforms, the accumulation of cAMP was monitored after an exposure time of 0, 5, 10, 15, 30, 60, 120 and 180 min. In addition, cAMP production was monitored for 0, 5, 10, 15 and 30 min following a 5 min exposure to FSH isoform fractions. Based on FSH measurements using radioimmunoassays, the less and mid-acidic isoforms caused almost twice as much cAMP to be accumulated than the acidic isoform fraction, thereby confirming an enhanced biological activity of FSH isoforms with a isoelectric point (pI) of >5.0. For all isoform fractions, maximal accumulation of cAMP was achieved after 30 min of exposure, after which the production declined to background levels. After a 5 min exposure to isoform fractions, levels of cAMP were significantly higher in the less acidic isoform fractions, but after isoform removal, the decline in cAMP production to background levels followed a similar time course. The results demonstrate that FSH isoforms with a pI of >5.0 induced significant biological responses within a period of 30 min and that prolonged exposure caused attenuated signal transduction. The present results, set in the context of the pulsatile characteristics of FSH release from the pituitary and the reported half-life of less acidic isoforms of approximately 35 min, make it conceivable that isoforms with a pI >5.0 actually possess important physiological functions during the periovulatory period.

[1]  W. Robertson,et al.  Improved FSH sensitisation and aromatase assay in human granulosa-lutein cells. , 2000, Molecular human reproduction.

[2]  V. Padmanabhan,et al.  Differential effects of the charge variants of human follicle-stimulating hormone. , 2000, Journal of Endocrinology.

[3]  W. Robertson,et al.  Do immunoassays differentially detect different acidity glycoforms of FSH? , 1999, Clinical endocrinology.

[4]  C. Timossi,et al.  Oestrogens regulate pituitary alpha2,3-sialyltransferase messenger ribonucleic acid levels in the female rat. , 1999, Journal of molecular endocrinology.

[5]  A. Byskov,et al.  FSH-induced resumption of meiosis in mouse oocytes: effect of different isoforms. , 1999, Molecular human reproduction.

[6]  A. Olivares,et al.  Receptor binding activity and in vitro biological activity of the human FSH charge isoforms as disclosed by heterologous and homologous assay systems , 1999, Endocrine.

[7]  C. Timossi,et al.  A less acidic human follicle-stimulating hormone preparation induces tissue-type plasminogen activator enzyme activity earlier than a predominantly acidic analogue in phenobarbital-blocked pro-oestrous rats. , 1998, Molecular human reproduction.

[8]  U. Vitt,et al.  Isoforms of human recombinant follicle-stimulating hormone: comparison of effects on murine follicle development in vitro. , 1998, Biology of reproduction.

[9]  S. McCann,et al.  Glycoform composition of serum gonadotrophins through the normal menstrual cycle and in the post-menopausal state. , 1998, Molecular human reproduction.

[10]  M. Rose Follicle stimulating hormone international standards and reference preparations for the calibration of immunoassays and bioassays. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[11]  C. Timossi,et al.  Structure-function relationship of follicle-stimulating hormone and its receptor. , 1998, Human reproduction update.

[12]  C. Timossi,et al.  A Naturally Occurring Basically Charged Human Follicle-Stimulating Hormone (FSH) Variant Inhibits FSH-Induced Androgen Aromatization and Tissue-Type Plasminogen Activator Enzyme Activity in vitro , 1998, Neuroendocrinology.

[13]  F. Maris,et al.  Prediction of the in vivo biological activity of human recombinant follicle stimulating hormone using quantitative isoelectric focusing. , 1997, Biologicals : journal of the International Association of Biological Standardization.

[14]  A. Hossaini,et al.  Cumulus cells of oocyte‐cumulus complexes secrete a meiosis‐activating substance when stimulated with FSH , 1997, Molecular reproduction and development.

[15]  V. Padmanabhan,et al.  Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion. , 1997, Endocrinology.

[16]  A. Ulloa-Aguirre,et al.  Studies on the relative in-vitro biological potency of the naturally-occurring isoforms of intrapituitary follicle stimulating hormone. , 1996, Molecular human reproduction.

[17]  R. de Leeuw,et al.  Structure-function relationship of recombinant follicle stimulating hormone (Puregon). , 1996, Molecular human reproduction.

[18]  B. Fauser Interference with follicle stimulating hormone regulation of human ovarian function. , 1996, Molecular human reproduction.

[19]  V. Padmanabhan,et al.  Follicle-stimulating isohormones: characterization and physiological relevance. , 1995, Endocrine reviews.

[20]  L. Díaz-Cueto,et al.  Dynamics of basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating hormone charge isoform distribution throughout the human menstrual cycle. , 1995, The Journal of clinical endocrinology and metabolism.

[21]  S. Chappel Heterogeneity of follicle stimulating hormone: control and physiological function. , 1995, Human reproduction update.

[22]  W. Crowley,et al.  Development of a bioassay for FSH using a recombinant human FSH receptor and a cAMP responsive luciferase reporter gene , 1994, Molecular and Cellular Endocrinology.

[23]  L. Wide,et al.  More basic forms of both human follicle-stimulating hormone and luteinizing hormone in serum at midcycle compared with the follicular or luteal phase. , 1993, The Journal of clinical endocrinology and metabolism.

[24]  M. Hearn,et al.  Isolation and physicochemical characterization of human follicle-stimulating hormone isoforms. , 1992, Endocrinology.

[25]  K. Dahl,et al.  FSH isoforms, radioimmunoassays, bioassays, and their significance. , 1992, Journal of andrology.

[26]  A. Cravioto,et al.  Biological characterization of the naturally occurring analogues of intrapituitary human follicle-stimulating hormone. , 1992, Human reproduction.

[27]  Morton B. Brown,et al.  Follicle-stimulating hormone signal transduction: Role of carbohydrate in aromatase induction in immature rat Sertoli cells , 1991, Molecular and Cellular Endocrinology.

[28]  M. Parmentier,et al.  Follitropin receptor down-regulation involves a cAMP-dependent post-transcriptional decrease of receptor mRNA expression , 1991, Molecular and Cellular Endocrinology.

[29]  K. McNatty,et al.  Effects of follicle stimulating hormone, cholera toxin, pertussis toxin and forskolin on adenosine cyclic 3',5'-monophosphate output by granulosa cells from Booroola ewes with or without the F gene. , 1990, Journal of reproduction and fertility.

[30]  L. L. Lang,et al.  Modulation of serum follicle-stimulating hormone bioactivity and isoform distribution by estrogenic steroids in normal women and in gonadal dysgenesis. , 1988, The Journal of clinical endocrinology and metabolism.

[31]  A. Ulloa-Aguirre,et al.  Immunological and biological potencies of the different molecular species of gonadotrophins. , 1988, Human reproduction.

[32]  P. Snyder,et al.  Similar isoelectric profiles of FSH from gonadotroph cell adenomas and non-adenomatous pituitaries. , 1986, Acta endocrinologica.

[33]  L. Wide Median charge and charge heterogeneity of human pituitary FSH, LH and TSH. II. Relationship to sex and age. , 1985, Acta endocrinologica.

[34]  G. Benker,et al.  Large-scale preparation of highly purified pyrogen-free human growth hormone for clinical use. , 1979, The Journal of endocrinology.